22: Lung defense mechanisms

protective mechanisms that can be conceptualized as different groups of components. Each appears to have a distinct role, but a tremendous degree of redundancy and interaction exists among different components. That the distal lung parenchyma is normally not infected serves as testimony to the effectiveness of the defense system. However, the protective mechanisms can break down, resulting in respiratory infection. Such a breakdown in defense can occur as a result of certain diseases, a large inoculum of microorganisms that overwhelms a normal host, an especially virulent organism, or frequently as a consequence of medical treatment that impairs the immune system.

Before the discussion of infectious disorders of the respiratory system in Chapters 23 through 27, it is appropriate to first consider how the lung protects itself against the infectious agents to which it is exposed. Although this chapter focuses on protective mechanisms against infection, defenses against noninfectious substances, especially inhaled particulate material, also are addressed. The major categories of defense mechanisms to be discussed include (1) physical or anatomic factors relating to deposition and clearance of inhaled material, (2) antimicrobial peptides, (3) phagocytic and inflammatory cells that interact with the inhaled material, and (4) adaptive immune responses, which depend on prior exposure to and recognition of the foreign material. The chapter concentrates on the aspects of the host defense system specific to the lung and then proceeds with a discussion of several ways the system breaks down, resulting in an inability to handle microorganisms and an increased risk for certain types of respiratory tract infection. The chapter concludes by briefly considering how we can activate or augment specific immune responses through immunization, thus enhancing defenses against selected respiratory pathogens.

Physical or anatomic factors

The pathway from the mouth or nose down to the alveoli requires that inhaled air traverse a series of progressively branching airways. The laminar flow of air through the airways becomes more turbulent at the branch points (subcarinae), thus enhancing deposition of particulate material on bronchial mucosal surfaces at these locations. Hence, inhaled particulates frequently are deposited at various points along the airway, never reaching the most distal region of lung, the alveolar spaces. Particle size is an important determinant of deposition along the airway and thus affects the likelihood of a particle’s reaching the distal parenchyma. When an inhaled particle is greater than 10 μm in diameter, it is likely to settle high in the upper airway (e.g., in the nose). For particles 5 to 10 μm in diameter, settling tends to occur somewhat lower, in the trachea or the conducting airways, but not down to the level of the small airways and alveoli. The particles most likely to reach the distal lung parenchyma range in size from 0.5 to 5 μm. Many bacteria fall within this size range, so deposition along the airways is not very effective for excluding bacteria from the lower respiratory tract. However, large particles of dust and other inhaled material are effectively prevented from reaching the distal lung parenchyma by virtue of their size. Of note, the target size for particles of inhaled medications, such as bronchodilators, is less than 5 μm so the medication can bypass the conducting airways and reach the more distal lung.

When particles are deposited in the trachea or bronchi, two major processes, cough and mucociliary transport, are responsible for physical removal of these particles from the airways. Cough is an important protective mechanism, frequently triggered by stimulation of airway irritant receptors, which are most prominent in the proximal airways and are activated by inhaled or aspirated foreign material. Rapid acceleration and high flow rates of air achieved by a cough are often effective in clearing irritating foreign material from the airways.

Factors affecting deposition and physical clearance of particles:

FIGURE 22.1 Schematic diagram of the cross-section of cilium. Two central

microtubules and nine pairs of peripheral microtubules are shown. A dynein arm

projects from each peripheral doublet, and nexin links and radial spokes provide

connections within microtubular structure. Source: (From Eliasson, R., Mossberg,

B., Camner, P., & Afzelius, B. A. (1977). The immotile-cilia syndrome. A

congenital ciliary abnormality as an etiologic factor in chronic airway infections

and male sterility. New England Journal of Medicine, 297, 1–6. Copyright 1977

Massachusetts Medical Society. All rights reserved.)

The movement of cilia on a particular cell and the movement between cells are strikingly coordinated, producing actual “waves” of ciliary motion. Exactly how such a pattern of ciliary motion is coordinated from cell to cell or even within the same cell is not entirely known. This wavelike motion accomplishes movement of the overlying mucous layer in a cephalad direction (i.e., from distal to more proximal parts of the tracheobronchial tree) at the remarkable estimated speed of 6 to 20 mm/min in the trachea. Inhaled particles that are trapped in the mucous layer are also transported upward and eventually either expectorated or swallowed.

Two layers comprise the mucous blanket bathing the epithelial cells. Directly adjacent to the cells is the sol layer, within which the cilia are located. The aqueous sol layer contains several molecules in solution that are part of the innate immune system and are discussed in the “Antimicrobial Peptides”